Modulation of HMGB1 Release in APAP-Induced Liver Injury: A Possible Strategy of Chikusetsusaponin V Targeting NETs Formation.

Autor:	Liu J; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Jiang M; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Jin Q; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Wu YL; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Cui ZY; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Cui BW; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Shang Y; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Zhan ZY; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Lin YC; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Jiao JY; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Piao MH; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Zhang ZH; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Sun RH; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China., Nan JX; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China.; Clinical Research Centre, Yanbian University Hospital, Yanji, China., Lian LH; Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University), State Ethnic Affairs Commission, Yanji, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China.; Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2021 Jul 21; Vol. 12, pp. 723881. Date of Electronic Publication: 2021 Jul 21 (Print Publication: 2021).
DOI:	10.3389/fphar.2021.723881
Abstrakt:	Acetaminophen (APAP), one of the most common antipyretic analgesics, which is safe at therapeutic dose, cause acute liver injury and even death at overdose. However, the mechanism of APAP-induced inflammation in liver injury is still controversial. Therefore, effective drug intervention is urgently needed. The aim of this study was to explore the inflammatory exact mechanism of APAP, especially on neutrophils, and to study the intervention effect of Chikusetsusaponin V (CKV) derived from Panax japonicus . Establishment of hepatotoxicity model of APAP in vitro and in vivo . In vitro , HepG2 cells, AML12 cells, primary mouse hepatocytes and neutrophils were used to mimic APAP-affected hepatocytes and neutrophil. In vivo , C57BL/6 mice were administrated overdose of APAP with or without neutrophil depletion or abolishing neutrophil extracellular traps (NETs) formation. In this study, APAP stimulation increased the level of HMGB1, IL-1β and Caspase-1 in mouse liver, especially hepatocytes, which had a synergistic effect with LPS/ATP combination. NETs were formatted at early stage of APAP or HMGB1-stimulated neutrophils' damage. Conditioned mediums from APAP-treated hepatocytes induced more significant NETs than direct APAP stimulation. Neutrophil depletion or abolishing NETs formation decreased HMGB1 level, eventually blocked hepatocytes necrosis. CKV pretreatment interfered Caspase-1 activation and HMGB1 release in APAP-damaged hepatocytes. CKV also prevented NETs formation. These results indicate that the production of HMGB1 may depend on the activation of Caspase-1 and play a key role in liver inflammation caused by APAP. The cross-dialogue between hepatocytes and neutrophils can be mediated by HMGB1. Therefore, CKV has a positive intervention effect on NETs-related inflammation in APAP-damaged liver, targeting Caspase-1-HMGB1. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Liu, Jiang, Jin, Wu, Cui, Cui, Shang, Zhan, Lin, Jiao, Piao, Zhang, Sun, Nan and Lian.)
Databáze:	MEDLINE
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